Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/ß+-thalassemia patient: a rare and challenging condition.

The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/ß(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/ß(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome.

Assessment of the uvulo-glossopharyngeal dimensions in patients with ß-thalassemia major.

OBJECTIVES: Thalassemia patients present varying degrees of craniofacial characteristics, while the morphology of the upper airway is less studied. The purpose of this study was to compare the uvula-glossopharyngeal dimensions (UGDs) of patients with ß-thalassemia major (BTM) with non-thalassemic subjects who had similarities in the maxillo-mandibular skeletal pattern. SUBJECTS AND METHODS: The material for this cross-sectional retrospective study consisted of lateral cephalograms of 40 BTM patients (23 males, 17 females, aged 9.5 ± 0.97 years). These were compared with lateral cephalograms of a control group of 40 non-thalassemic subjects (23 males, 17 females, aged 11.0 ± 0.87 years). The control group was chosen so that they had similarities with the BTM patients in the following cephalometric variables: SNA (in degree), SNB (in degree), ANB (in degree), and anterior facial height (N-Me). RESULTS: The following UGDs in thalassemic subjects were significantly shorter in patients with BTM: tongue length (P < 0.05), the distance between the hyoid bone and the mandibular plane (P < 0.01), and the vertical distance between hyoid bone and the C3-RGN line (line connecting third vertebra and retrognathion) (P < 0.05). The middle airway space in BTM patients was significantly wider (P < 0.05), and a trend was observed for the wider inferior airway space (P = 0.07). CONCLUSIONS: Based on this study, some UGDs in BTM patients were significantly different, compared to non-thalassemic subjects who had a similar maxillo-mandibular skeletal pattern. These findings may have implications for the long-term treatment of BTM patients; however, since groups were not exactly age-matched, the observed differences between groups could be attributed to either BTM, age, or both. Additional studies with age-matched subjects are needed to investigate the relationship between BTM and UGDs.

Spontaneous osteonecrosis of the jaw in a ß-Thalassemia intermedia patient.

The resultant anemia in hemoglobinopathies like thalassemia can lead to expansion of the bone marrow cavities due to compensatory hyperplasia. This article reports a case of spontaneous osteonecrosis of the left maxillary alveolus in a patient with ß-Thalassemia intermedia. The area affected presented as areas of osteosclerosis on the radiographic examination and sequestrectomy of the left maxillary alveolus was performed after consultation with his hematologist. The exact pathogenesis for the osteonecrosis is unclear. One possible postulation for the cause of osteonecrosis in our case could be that the alveolar bone suffered ischemic infarction secondary to occlusion of the microvasculature within the expanded cancellous bone.

Nephrectomy Does not Exacerbate Cancellous Bone loss in Thalassemic Mice.

Patients with ß-thalassemia have an increased risk of developing chronic kidney disease which is associated with osteoporosis and periodontitis. The purpose of this study was to evaluate mandibular and femoral bone change in heterozygous ß-globin knockout (BKO) mice following 5/6 nephrectomy (Nx). Female and male BKO mouse blood smears demonstrated microcytic hypochromic anemia. Serum urea nitrogen, creatinine, calcium, and phosphorus levels were not changed in BKO mice. Nx increased the serum levels of urea nitrogen in both wild type (WT) and BKO mice and the level was much higher in BKO males. Serum level of creatinine was increased in Nx WT but not BKO mice. However, serum calcium and phosphorus levels were not altered. Nx induced comparable renal fibrosis in BKO mice and WT controls. Bone loss was observed in mandibular cancellous bone but not cortical bone of both male and female BKO mice. Nx decreased cancellous bone volume and cortical thickness in WT. Interestingly, BKO mice were resistant to Nx-induced cancellous bone loss. However, cortical thickness and cortical bone mineral density were reduced in Nx male BKO mice. Nx increased mRNA levels of type I collagen, Osx and Trap in WT but not BKO mice. Similarly, Nx reduced cancellous bone volume in femurs and increased osteoblast number and osteoclast number in WT not BKO mice. Serum FGF23 and erythropoietin levels were markedly increased in BKO mice. Nx decreased serum erythropoietin but not FGF23 levels. Since WT treated with erythropoietin exhibited a significant reduction in cancellous bone volume, it was possible that lower level of erythropoietin in Nx BKO mice prevented the Nx-induced cancellous bone loss.

A pilot beta-thalassaemia screening program in the Albanian population for a health planning program.

In Albania, no definite national screening programme of beta-thalassaemia has yet been developed for carrier detection. Only limited information about the occurrence and the types of haemoglobin abnormalities is available. Thus, an educational and screening programme was carried out in one high school with a total of 217 young students from the coastal province of Lushnja in Albania. The pilot programme included a systematic sampling of whole saliva, DNA genomic extraction and the determination of defective beta-thalassaemia genes by reverse dot-blot hybridization with 22 probes specific for the Mediterranean populations.Of the 201 subjects tested, 17 (8.4%) students turned out to be carriers of beta-thalassaemia mutations and haemoglobin variants. The most common mutation is HbS (c.20A-->T) with a frequency of 3.2%, followed by IVS-I-110 (G-->A) (c.93-21G-->A) substitution identified in 4 out of 402 chromosomes (1%). In the province of Lushnja, the frequency of beta-thalassaemia carriers was high. As expected, the results show that identified mutations in this population are similar to those found in the east Mediterranean area, suggesting the same origin for mutant alleles during migratory streams. Implementation of a routine carrier-screening programme is significantly facilitated by the presence of only two mutations and would be a wise approach to prevent beta-thalassaemia in the region.

[A family survey of syndromes of traditional Chinese medicine in patients with beta-thalassemia].

OBJECTIVE: To explore the relationship between syndromes of traditional Chinese medicine (TCM) and genetic background in patients with beta-thalassemia. METHODS: TCM syndromes were surveyed in the selected 78 patients with beta-thalassemia intermedia including 120 parents. The gene mutations were detected separately. The frequency and score of TCM syndromes between the offspring and their parents in different family types were analyzed, and the differences were compared. RESULTS: The 73 families were divided into two family types by hereditary characteristics. Family type one meant that genotypes of one of the parents were normal, while the offspring genotypes were heterozygous and were exactly the same as another parent. In the 22 families of type one, the heterozygous offspring manifested 6 high-frequency symptoms and signs such as spontaneous perspiration, dry mouth and dry throat, pale or sallow complexion, tidal fever and night sweating, lassitude and pale fingernails. The heterozygous parents manifested 5 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs, tinnitus, dry mouth and dry throat. The normal parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, and spontaneous perspiration. TCM syndrome score in the heterozygous offspring was higher than that in the heterozygous and normal parents, but there was no significant difference (P>0.05). Family type two meant that genotypes of both parents were heterozygous, while the offspring genotypes were heterogenic duplex heterozygotes. In the 51 families of type two, the offspring manifested 9 high-frequency symptoms and signs such as pale or sallow complexion, spontaneous perspiration, dry mouth and dry throat, pale fingernails, tidal fever and night sweating, lassitude, frequent attack of common cold, dysphoria with feverish sensation in chest, and yellow discoloration of the skin and sclera. The parents manifested 3 high-frequency symptoms and signs such as lassitude in loins and knees, dizziness, aversion to cold and cold limbs. TCM syndrome score in the offspring was significant higher than that in the parents (P<0.01). CONCLUSION: In the two family types, TCM syndrome in the offspring is of yin-blood deficiency, while the syndrome of the parents is of kidney deficiency. The differences of TCM syndromes between the offspring and the parents may have some relations to the type of mutant genes and genetically modified ingredients. This research provides scientific evidence to TCM syndrome differentiation treatment of thalassemia.

Comparative evaluation of oral and dento-maxillofacial manifestation of patients with sickle cell diseases and beta thalassemia major.

BACKGROUND: Regarding the importance of oral and dental health in patients with hemoglobinopathies and also due to the different results of different studies in this background, in patients with beta thalassemia (BTM) and sickle cell disease (SCD), this study aimed to evaluate and compare the oral and dental manifestations of patients with BTM and SCD. MATERIAL AND METHODS: In this cross-sectional study during the years 2014-2017, a total of 175 patients (with documented BTM or SCD attending to Tehran, Mashhad, Isfahan, and Tabriz cities central hospitals) were randomly recruited. Required information was gathered through a thorough physical examination of the oral cavity in a private office and a face-to-face interview by an orthodontist and two dentists. Data were analyzed using SPSS version 22.0. RESULTS: In general, 120 diagnosed patients with BTM (88 males and 32 females) and 55 patients with SCD (25 males and 30 females) attending to Iran largest cities, central hospitals were randomly recruited. We found a significantly higher prevalence (p < .05) of some oral manifestations among the BTM patients (Gingival Index = 2.18 ± 1.300, 1.64 ± 0.963; Decayed teeth = 8.31 ± 3.330, 2.33 ± 1.221; Missing teeth = 3.51 ± 2.016, 1.19 ± 0.820; DMFT = 13.92 ± 7.001, 2.63 ± 1.301) than the apparently healthy people. CONCLUSION: Finally, the study gives an insight into the various oral and dento-maxillofacial manifestations of SCD and BTM and also reveals an association that exists between the oral and dento-maxillofacial manifestations and systemic health in these patients, thus stressing the importance of the concise and periodic examination of these individuals to perform appropriate preventive dental and periodontal care, and the facilitation of the management of the disease.

Efficacy of Interferon A-2b monotherapy in Β-thalassemics with chronic hepatitis C.

BACKGROUND & AIMS: Monotherapy with standard or pegylated interferon (PegIFN) remains the first-line treatment for HCV infection in patients with thalassemia major (ßTM), although its long-term impact is still unknown. We aimed to assess the efficacy of IFN-a2b/PegIFN-a2b (one or multiple treatment sessions) and the predictors for sustained virological response (SVR) in HCV-infected ßTM patients. METHODS: Between 11/1992 and 12/2013 [median follow-up: 165.5 months (8-237)], 48 ßTM HCV-infected patients [19 males, median age: 22 years (12-45)], received IFN-a2b (n=34) or PegIFN-a2b (n=14). Twenty-three patients (47.9%) had a previous splenectomy; 13/40 (32.5%) patients had Ishak stage >/=4 and 21/40 (52.5%) had siderosis grade 3-4. HCV-genotype was available in 36 patients (genotype 1: 47.2%, 2: 5.6%, 3: 25%, and 4: 22%). IL28B genotype was determined in 37 patients by means of in-house real-time PCR (CC: 27%, CT: 62.2%, TT: 10.8%). RESULTS: Totally, 15/48 (31.3%) achieved SVR following the first treatment and 18/48 (37.5%) after multiple courses. Splenectomy (p=0.01) and fibrosis grade >/=4 (p<0.05) were negative predictors for SVR (first course), whereas splenectomy (p<0.05) and age >18 (p<0.02) for SVR after multiple courses. In HCV-genotype 1/4 (n=25), none of the patients with CT or TT IL28B genotype achieved SVR compared to 50% of the CC patients (p=0.004). CONCLUSIONS: Interferon is an effective therapeutic option in HCV-infected ßTM patients. IL28B genotype was a strong predictor for SVR, together with splenectomy, age and fibrosis.

Predictive value of MCV/RBC count ratio to discriminate between iron deficiency anaemia and beta thalassaemia trait.

AIM AND BACKGROUND: Two forms of hypochromic microcytic anaemia i.e. iron deficiency and beta-thalassaemia trait are common in our society. This study reports the prevalence of iron deficiency anaemia and beta-thalassaemia trait and predictive value of MCV/RBC count ratio to discriminate between two. METHODS: Venous blood was taken from 299 students of Karachi Medical & Dental College and Ziauddin Medical University in Na2 EDTA and analyzed by semi-automated Sysmex K-1000 haematology analyzer. MCV/RBC count ratio was used to discriminate between iron deficiency and beta-thalassaemia trait and > 14% was marked as iron deficiency. Hb electrophoresis was used as gold standard test for confirmation. Serum iron and TIBC was performed to confirm iron deficiency anaemia. RESULTS: Iron deficiency was found in 9% while beta-thalassaemia was seen in 3% students. MCV/RBC count ratio showed a positive predictive value of 91%. CONCLUSIONS: In areas where iron deficiency anaemia and beta-thalassaemia trait are common, MCV/RBC count ratio can be used to screen out beta-thalassaemia trait.

Spatially addressable bead-based biosensor for rapid detection of beta-thalassemia mutations.

A simple glass-polymer bead-based biosensor was validated for the detection of beta-thalassemia mutations. Different bead types, each carrying allele-specific probes targeting a particular mutation on the beta-globin gene, were immobilized and distinguished on the chip based on their spatial addresses. Genomic DNA samples carrying various single nucleotide transitions and transversions in the beta-globin gene were subjected to polymerase chain reaction and asymmetric amplification in the presence of Cy3-labeled primers, followed by hybridization onto the chip and detection under an epifluorescent microscope. Mutations that were heterozygous or homozygous were easily detected on the device based on the signal intensity difference (or similarity) between the wildtype and mutant probes. This device successfully detected all six common beta-globin gene mutations within 30 min. The number of targeted mutations on this chip can be easily expandable through the introduction of additional probe sets.

Development of new substrates for high-sensitive genotyping of minority mutated alleles.

An unsurpassed level of sensitivity was reached in the detection of minority mutated alleles. A low-density microarray was printed on a substrate specifically designed to provide an interference effect which amplifies the collection of the light emitted on the support and reinforces the intensity of excitation light. Optimal performance of the array was obtained by maximizing the probe density and the binding efficiency to the target through a polymeric coating made by the adsorption of a copolymer of N,N-dimethylacrylamide (97% of moles), N,N-acryloyloxysuccinimide (2%) and 3-(trimethoxysilyl)propyl methacrylate (1%) synthesized by free radical copolymerization. The new substrate was used in the identification of fetal mutations in the maternal plasma DNA. Amino-modified amplicons from genomic DNA corresponding to the locus of eight beta-thalassemia mutations were immobilized and interrogated with dual-color oligonucleotide targets. Compared with the conventional glass substrates, the new substrate showed a great enhancement of fluorescence signals thanks to the combination of the optics with the highly efficient polymeric coating, allowing specific detection of all mutations. The high sensitivity and selectivity obtained made it possible to develop assays for the identification of paternally inherited mutations on fetal DNA in the maternal plasma in couples at risk for beta-thalassemia.

Fast and sensitive diagnosis of thalassemia by capillary electrophoresis.

This paper demonstrates the diagnosis of beta-thalassemia by capillary electrophoresis in conjunction with laser-induced fluorescence using poly(ethylene oxide) (PEO) solutions in the presence of electroosmotic flow (EOF). During the electrophoretic separation, PEO solution entered a capillary from the anodic vial by EOF. The separation of a mixture of the polymerase chain reaction (PCR) products (330 and 334 base pairs) from a healthy person and a beta-thalassemia patient was accomplished within 15 min at 15 kV using 1.5% PEO containing 2 M urea at 30 degrees C. The electropherogram patterns instead of migration times were used to diagnose beta-thalassemia, with an accuracy of 100% for the analyses of 11 blood samples from suspected patients. After injecting a large volume of the mixture to the capillary filled with 800 mM Tris-borate buffer (pH 10.0), the DNA fragments stacked due to increases in viscosity and sieving when migrating into 1.5% PEO solution. As a result of improved sensitivity, only 15 PCR cycles were required when using 500 ng of DNA templates. The results shown in this study indicate the potential of this simple, rapid, and cost-effective method for the diagnosis of beta-thalassemia.

Talassemia: características clínicas e radiográficas de interesse odontológico / Thalassemia: essential radiographic and clinical features of interest to dentistry

A talassemia é um tipo de anemia hereditária que afeta predominantemente indivíduos nascidos ou descendentes de países banhados pelo Mar Mediterrâneo, como Itália e Grécia. Também conhecida como anemia de Cooley e anemia mediterrânea, a doença provoca alterações na formação da hemoglobina e malformações do crânio, ossos longos, maxila e mandíbula. Apresenta dois quadros clínicos distintos: um grave, chamado de talassemia "maior", e outro leve, denominado talassemia "menor". O exame hematológico diagnostica as duas formas da doença. Suas manifestações clínicas e radiográficas incluem hepatoesplenomegalia, linfadenopatia, aumento da mandíbula, aumento dos espaços medulares, trabéculas ósseas espessas e em menor quantidade, lembrando "teia de aranha", deslocamento do canal mandibular com perda de detalhe de suas corticais superior e inferior e aspecto radiográfico de "cabelos em pé" na superfície do crânio. Algumas dessas manifestações são tão características e passíveis de serem observadas em radiografias que fazem parte da rotina do cirurgião-dentista. Neste relato de caso, são discutidas as alterações observadas na radiografia panorâmica de uma paciente com talassemia diagnosticada por meio de exame hematológico.

Thalassemia is a type of hereditary anemia that predominantly affects individuals born in or descendents of countries bathed by the Mediterranean Sea, such as Italy and Greece. Also known as Cooley's anemia and Mediterranean anemia, the disease causes alterations in hemoglobin formation and malformations of the cranium, long bones, maxilla and mandible. It presents two distinct clinical conditions: one severe, called "major" thalassemia, and the other mild, denominated "minor" thassalemia. Hematologic exam diagnoses the two forms of the disease. Its clinical and radiographic manifestations include hepatosplenomegalia, lymphadenopathy, augmented mandible, increase in medullary spaces, thick bone trabeculae and in lower quantity, resembling a "spider web", displacement of the mandibular canal, with loss of detail of its superior and inferior corticals and a radiographic aspect of "hair standing on end" at the surface of the cranium. Some of these manifestations are so characteristic and capable of being observed in radiographs that they form part of the dentist's routine. This case report discusses the alterations observed in the panoramic radiograph of a patient with thalassemia diagnosed by means of hematologic exam.